Paola Arlotta on her Career Trajectory, Why Science Needs Philanthropy, and Equity in STEM

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Most people know Paola Arlotta, PhD, Professor and Chair of the Department of Stem Cell and Regenerative Biology at Harvard University, for her seminal contributions to our understanding of mammalian brain development. But fewer know about her path to becoming an accomplished developmental neuroscientist, or her fierce advocacy for equity in STEM.

As one of the earliest recipients of our a NYSCF – Robertson Stem Cell Investigator Awards, we recently recruited Dr. Arlotta as our Scientific Advisor for all of our extramural grant awards. These grant programs, uniquely enabled by private philanthropy, support high-risk, high-reward research at critical points in the careers of scientists (NYSCF–Druckenmiller Awards for postdoctoral fellows, and the NYSCF–Robertson Awards for early career investigators). Now a year into her new role, we sat down with Paola to discuss her scientific trajectory, the transformative impact of philanthropic funding on research, and her full-circle journey to shaping the future of an award that changed her career.

A Non-Linear Career Path

Born and raised in Italy, Dr. Arlotta’s interest in science was sparked by a fascination for the natural world, which later on inspired her to earn a masters in biochemistry and a Ph.D. in molecular biology. During her masters, she discovered a passion for developmental biology (i.e. how embryos develop the sophisticated tissues and organs that make up our bodies), but it wasn’t until she was a postdoctoral trainee at Harvard Medical School that she decided to pursue the field as her main area of research.

“My career trajectory has not been linear. I’ve always known that I had a passion for science, and for asking questions about the natural world, but I wasn’t sure about what scientific field I really liked,” she explained. “I tried a lot of different things before I got to do the things that I became passionate about, and I think that’s ok. I say this because many people have a direct, very precise path to what they do in the future, and mine was not.”

“I could have studied any tissue, but I happened to look at the brain, and one peek was enough to hook me,” she recalled. “I love this tissue — it is the part in our body that makes us human. Once I began to study how the mammalian brain develops,  I couldn’t stop.”

Technology Paves the Way for a Disease Focus

In 2007, Dr. Arlotta opened her lab, motivated by understanding how the cerebral cortex (the part of our brain that controls how we sense, move, and think) is formed and assembled during embryonic development. She started studying this process using rodents as model systems, but ran into a few roadblocks.

“It became very clear to myself and the rest of the field that there is only so much that we can learn about the development of our own brain by studying other species,” she said. “There are parts of the human brain that are developed much more than in other animals, and especially in the cerebral cortex there are huge differences between species.”

However, it took some time – and two major technological breakthroughs – for Dr. Arlotta and others to venture into human models. First, induced pluripotent stem cell technology, invented in 2006, made it possible for scientists to create any tissue of the body starting from a stem cell, which in turn can be generated from something as simple as a blood sample.

“Stem cell technology showed us that many different developmental processes can occur outside of the context of an embryo, and we can study them in a dish,” she explained.

Second, major advances in DNA sequencing and cellular imaging made it possible to interrogate both genes and cells at an unprecedented scale — and for the first time, scientists did not need prior knowledge of the cells and tissues being studied to use these technologies.

“We went from studying a few cells and a few genes at a time to studying everything all at once,” she remarked.

Since then, her group has pioneered another transformative technology:  using human stem cells to build avatars of the cerebral cortex known as cortical organoids and applied them to study how human neurodevelopmental diseases like autism spectrum disorder and psychiatric illnesses emerge.

“We have been leveraging genetic information from patients with autism spectrum disorder and neuropsychiatric diseases to introduce genetic modifications to human organoid models and ask how they impact the development of the human brain. This opens a whole new path of investigation to develop therapeutics for these diseases. We couldn’t do this even a few years ago.”

An Enabling and Inspiring Career Award

In 2011, four years after establishing her own lab, Dr. Arlotta was awarded a NYSCF – Robertson Stem Cell Investigator grant, which provides unrestricted funding to catalyze the careers of rising stars in the field. This marked a turning point in her career and her research, shifting the focus of her lab to study human brain diseases.

“Thanks to this unique grant, I was able to transition from being a very basic developmental neurobiologist to beginning to think about the human brain and disease. The word ‘disease’ was not in my program before,” she reflected. “If not for the award, my disease focus would have happened much later, or not at all.”

“I would say the award was enabling: it allowed me to address different research questions about the brain, and then when technology and advances in stem cell biology, like the organoids, were available to address these questions, I could hit the ground running,” she continued.

“Moreover, I see these awards as inspirational, because it is very rare to receive a grant of this prestige and size at the start of your career as junior faculty. That inspires you to do the best science possible, and realize that the only limitation to great discovery is you. This is very liberating for a scientist.”

How Philanthropy Fuels Innovation

Most traditional grant mechanisms fund specific research projects that have been de-risked by years of groundwork, leading to incremental advances in knowledge. In contrast, grant programs driven by private philanthropy, like the NYSCF–Robertson Investigator Awards, can bet on bolder and riskier ideas put forth by emerging talent, and potentially provide proof of concept for a completely new idea or technology that can ultimately transform the field.

“I like to think about how a field is innovated. Fundamentally, innovation is of two types: you can innovate by adding new pieces of knowledge to a field progressively, or you can innovate by inventing something completely new – e.g. bringing in better technologies that can transform the field, or making a discovery that changes the conceptual framework of how we think about a biological process,” remarked Dr. Arlotta. “I love the latter because it allows you to make a jump into the future.”

“For that to happen, you need to have a certain level of imagination and talent, but you also need to have the support of a community that values that kind of high-risk science,” she continued.

Dr. Arlotta underscored the value of philanthropic funding and career-level awards to free scientists from the constraints of specific projects, technologies, or directions.

“Philanthropic funding is absolutely critical in science. The idea that you can put in place the best possible selection process for the scientists rather than the science, and trust the scientists to decide where the science is going is priceless. It allows you to be free to do the best science that you can,” she emphasized.

“Because the scientists awarded these NYSCF – Robertson Investigator grants are visionary and want to change the field and the face of health, it allows them to put in place high-risk, high-reward projects. If it works out, the field is leaping forward instead of just progressing one step at a time.”

The Power of Community

Discoveries are rarely made in a silo – it usually takes many different minds and ideas to move science forward. Dr. Arlotta emphasized the importance of building connections with other scientists not only to improve her own work but also to catalyze progress in the field.

“Your community of scientists is very important to shape your way of thinking about your work. Every time I have a constructive discussion with other scientists, something really powerful comes out on the other end that I can’t predict before I have these interactions,” she noted.

The emphasis on team science is ingrained in NYSCF’s mission, and one of the most unique benefits of receiving the NYSCF – Robertson Investigator Award is joining the NYSCF Innovator Community, a global group of over 200 outstanding early career scientists and postdoctoral fellows based at institutions around the world.

NYSCF Innovators gather at the retreat

“What NYSCF does really well is to bring people together. There are a lot of opportunities for these kinds of interactions, and then naturally, a lot of collaborations emerge,” she continued.

There are many examples of how this community, through coming together and discussing science, has established productive collaborations. Dr. Arlotta mentioned her own with other NYSCF – Robertson Investigators and MIT’s Ed Boyden, PhD on expansion microscopy and Feng Zhang, PhD, on CRISPR technology, but also others that have inspired her, such as the collaboration between NYSCF’s Valentina Fossati, PhD and Paul Tesar, DPhil, of Case Western Reserve University School of Medicine​.

Dr. Arlotta also stressed the unique value that the NYSCF Innovator Community brings by converging the neuroscience and stem cell biology fields.

“At the annual retreat, we would hear this mix of talks in both neuroscience and stem cell biology. By being there together and discussing each other’s work, we began to speak a similar language. All of the science that came out of the intersection of these two fields was very unique and exciting.”

Advancing Equity in STEM through Leadership and Advocacy

“In science, especially when we are trying to answer really complex questions, you want as much diversity of opinion, thought, and ideas as you possibly can. You want as much cross-pollination among individuals that have had different experiences as possible,” Dr. Arlotta reflected.

Achieving equity in STEM is a mission close to Dr. Arlotta’s heart, and our shared interest in this has sparked years of collaboration with NYSCF. She shared how she prioritizes these issues in her leadership roles, from individual to institutional approaches.

“At the individual level, I have the responsibility to serve as a role model for people in the community that can recognize themselves in somebody like me.”

“I actually talk a lot about the mistakes I made, and about the fact that there are different ways to be successful in science, and you need to choose your own way. I think there is huge value in seeing someone more senior, someone that you can recognize yourself in and that has faced similar challenges before you,” she continued.

Scientists convene at IWISE’s first meeting

Dr. Arlotta’s commitment to equity prompted her to join the Initiative on Women in Science and Engineering (IWISE), an initiative launched by NYSCF’s CEO Susan Solomon in 2014 to address gender inequity in STEM. She was part of IWISE’s inaugural working group that defined actionable strategies  with the greatest potential to advance women in the scientific community, especially into leadership roles.

“Now, the strategies we devised in IWISE can be the foundation for more activities that expand beyond women to a wider range of minoritized individuals to create a diverse community,” she explained. I feel that NYSCF, including the NYSCF awards, have been particularly focused on this aspect of science.”

In her new role as NYSCF’s Scientific Advisor for extramural grant programs, Dr. Arlotta is contributing her knowledge and experience both as a leader and awardee to ensure that these awards support outstanding talent from diverse backgrounds.

“As part of the review process for the Robertson Investigator awards, we have been implementing the idea that what scientists are doing to make our community a better and more diverse place is valued alongside their scientific achievements. Diversity and inclusion efforts are valuable for making a better community, and we want to recognize them,” she concluded.

“As scientists, we need to make those discoveries that innovate the field and make the world a better place. But we also need to foster a community that is diverse and meaningful.”

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